Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O‑Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product
We describe the synthesis of 10-aza-9-oxakalkitoxin, an N,N,O-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH2- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays po...
Gespeichert in:
| Veröffentlicht in: | Journal of the American Chemical Society 2020-05, Vol.142 (20), p.9147-9151 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 9151 |
|---|---|
| container_issue | 20 |
| container_start_page | 9147 |
| container_title | Journal of the American Chemical Society |
| container_volume | 142 |
| creator | Dhanju, Sandeep Upadhyaya, Kapil Rice, Christopher A Pegan, Scott D Media, Joseph Valeriote, Frederick A Crich, David |
| description | We describe the synthesis of 10-aza-9-oxakalkitoxin, an N,N,O-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH2- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays potent and selective cytotoxicity (IC50 2.4 ng mL–1) comparable to that of kalkitoxin itself (IC50 3.2 ng mL–1) against the human hepato-carcinoma cell line HepG2 over both the human leukemia cell line CEM and the normal hematopoietic CFU-GM. Like kalkitoxin, and contrary to the common expectation for hydroxylamines, 10-aza-9-oxakalkitoxin is not mutagenic. |
| doi_str_mv | 10.1021/jacs.0c03763 |
| format | Article |
| fullrecord | <record><control><sourceid>acs_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1021_jacs_0c03763</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>a110656302</sourcerecordid><originalsourceid>FETCH-LOGICAL-a324t-abd42ae1577223922c56066e108a65e8c593833bca774e9e3edde6e5d77b8de83</originalsourceid><addsrcrecordid>eNptkE1OwzAQhS0EoqWwY428ZJGAfxI7WVYVFKTSIgHraBK7kDaNK9uRGlZcgRNwN05CoxZWrEZv3jdPmofQOSVXlDB6vYDCXZGCcCn4AerTmJEwpkwcoj4hhIUyEbyHTpxbbGXEEnqMepxxEUmS9tHXU1v7N-1KF-BR6403m7IofRtgqBUe6_pvg80cUxIO3yFMQ7OBJVTLsjPrjsXTYBrMvj8-n23pmtz50jdeK3zXKms2bQWrstZ4WENlXgNs7N7YyzkG_AC2Q6bgGwsVfrRGNYU_RUdzqJw-288Berm9eR7dhZPZ-H40nITAWeRDyFXEQNNYSsZ4ylgRCyKEpiQBEeukiFOecJ4XIGWkU821UlroWEmZJ0onfICCXW5hjXNWz7O1LVdg24ySrOs563rO9j1v8Ysdvm7ylVZ_8G-xW-ByB3RXC9PY7efu_6wf91eJWw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O‑Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Dhanju, Sandeep ; Upadhyaya, Kapil ; Rice, Christopher A ; Pegan, Scott D ; Media, Joseph ; Valeriote, Frederick A ; Crich, David</creator><creatorcontrib>Dhanju, Sandeep ; Upadhyaya, Kapil ; Rice, Christopher A ; Pegan, Scott D ; Media, Joseph ; Valeriote, Frederick A ; Crich, David</creatorcontrib><description>We describe the synthesis of 10-aza-9-oxakalkitoxin, an N,N,O-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH2- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays potent and selective cytotoxicity (IC50 2.4 ng mL–1) comparable to that of kalkitoxin itself (IC50 3.2 ng mL–1) against the human hepato-carcinoma cell line HepG2 over both the human leukemia cell line CEM and the normal hematopoietic CFU-GM. Like kalkitoxin, and contrary to the common expectation for hydroxylamines, 10-aza-9-oxakalkitoxin is not mutagenic.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/jacs.0c03763</identifier><identifier>PMID: 32364709</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Biological Products - chemical synthesis ; Biological Products - chemistry ; Biological Products - pharmacology ; Cell Line ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Drug Screening Assays, Antitumor ; Humans ; Molecular Structure</subject><ispartof>Journal of the American Chemical Society, 2020-05, Vol.142 (20), p.9147-9151</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a324t-abd42ae1577223922c56066e108a65e8c593833bca774e9e3edde6e5d77b8de83</citedby><cites>FETCH-LOGICAL-a324t-abd42ae1577223922c56066e108a65e8c593833bca774e9e3edde6e5d77b8de83</cites><orcidid>0000-0003-2400-0083 ; 0000-0002-0920-0784 ; 0000-0002-2958-5319</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jacs.0c03763$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jacs.0c03763$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2763,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32364709$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dhanju, Sandeep</creatorcontrib><creatorcontrib>Upadhyaya, Kapil</creatorcontrib><creatorcontrib>Rice, Christopher A</creatorcontrib><creatorcontrib>Pegan, Scott D</creatorcontrib><creatorcontrib>Media, Joseph</creatorcontrib><creatorcontrib>Valeriote, Frederick A</creatorcontrib><creatorcontrib>Crich, David</creatorcontrib><title>Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O‑Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>We describe the synthesis of 10-aza-9-oxakalkitoxin, an N,N,O-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH2- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays potent and selective cytotoxicity (IC50 2.4 ng mL–1) comparable to that of kalkitoxin itself (IC50 3.2 ng mL–1) against the human hepato-carcinoma cell line HepG2 over both the human leukemia cell line CEM and the normal hematopoietic CFU-GM. Like kalkitoxin, and contrary to the common expectation for hydroxylamines, 10-aza-9-oxakalkitoxin is not mutagenic.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological Products - chemical synthesis</subject><subject>Biological Products - chemistry</subject><subject>Biological Products - pharmacology</subject><subject>Cell Line</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Humans</subject><subject>Molecular Structure</subject><issn>0002-7863</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkE1OwzAQhS0EoqWwY428ZJGAfxI7WVYVFKTSIgHraBK7kDaNK9uRGlZcgRNwN05CoxZWrEZv3jdPmofQOSVXlDB6vYDCXZGCcCn4AerTmJEwpkwcoj4hhIUyEbyHTpxbbGXEEnqMepxxEUmS9tHXU1v7N-1KF-BR6403m7IofRtgqBUe6_pvg80cUxIO3yFMQ7OBJVTLsjPrjsXTYBrMvj8-n23pmtz50jdeK3zXKms2bQWrstZ4WENlXgNs7N7YyzkG_AC2Q6bgGwsVfrRGNYU_RUdzqJw-288Berm9eR7dhZPZ-H40nITAWeRDyFXEQNNYSsZ4ylgRCyKEpiQBEeukiFOecJ4XIGWkU821UlroWEmZJ0onfICCXW5hjXNWz7O1LVdg24ySrOs563rO9j1v8Ysdvm7ylVZ_8G-xW-ByB3RXC9PY7efu_6wf91eJWw</recordid><startdate>20200520</startdate><enddate>20200520</enddate><creator>Dhanju, Sandeep</creator><creator>Upadhyaya, Kapil</creator><creator>Rice, Christopher A</creator><creator>Pegan, Scott D</creator><creator>Media, Joseph</creator><creator>Valeriote, Frederick A</creator><creator>Crich, David</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0003-2400-0083</orcidid><orcidid>https://orcid.org/0000-0002-0920-0784</orcidid><orcidid>https://orcid.org/0000-0002-2958-5319</orcidid></search><sort><creationdate>20200520</creationdate><title>Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O‑Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product</title><author>Dhanju, Sandeep ; Upadhyaya, Kapil ; Rice, Christopher A ; Pegan, Scott D ; Media, Joseph ; Valeriote, Frederick A ; Crich, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a324t-abd42ae1577223922c56066e108a65e8c593833bca774e9e3edde6e5d77b8de83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological Products - chemical synthesis</topic><topic>Biological Products - chemistry</topic><topic>Biological Products - pharmacology</topic><topic>Cell Line</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Humans</topic><topic>Molecular Structure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dhanju, Sandeep</creatorcontrib><creatorcontrib>Upadhyaya, Kapil</creatorcontrib><creatorcontrib>Rice, Christopher A</creatorcontrib><creatorcontrib>Pegan, Scott D</creatorcontrib><creatorcontrib>Media, Joseph</creatorcontrib><creatorcontrib>Valeriote, Frederick A</creatorcontrib><creatorcontrib>Crich, David</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dhanju, Sandeep</au><au>Upadhyaya, Kapil</au><au>Rice, Christopher A</au><au>Pegan, Scott D</au><au>Media, Joseph</au><au>Valeriote, Frederick A</au><au>Crich, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O‑Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product</atitle><jtitle>Journal of the American Chemical Society</jtitle><addtitle>J. Am. Chem. Soc</addtitle><date>2020-05-20</date><risdate>2020</risdate><volume>142</volume><issue>20</issue><spage>9147</spage><epage>9151</epage><pages>9147-9151</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><abstract>We describe the synthesis of 10-aza-9-oxakalkitoxin, an N,N,O-trisubstituted hydroxylamine-based analog, or hydroxalog, of the cytotoxic marine natural product kalkitoxin in which the -NMe-O- moiety replaces a -CHMe-CH2- unit in the backbone of the natural product. 10-Aza-9-oxakalkitoxin displays potent and selective cytotoxicity (IC50 2.4 ng mL–1) comparable to that of kalkitoxin itself (IC50 3.2 ng mL–1) against the human hepato-carcinoma cell line HepG2 over both the human leukemia cell line CEM and the normal hematopoietic CFU-GM. Like kalkitoxin, and contrary to the common expectation for hydroxylamines, 10-aza-9-oxakalkitoxin is not mutagenic.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>32364709</pmid><doi>10.1021/jacs.0c03763</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0003-2400-0083</orcidid><orcidid>https://orcid.org/0000-0002-0920-0784</orcidid><orcidid>https://orcid.org/0000-0002-2958-5319</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0002-7863 |
| ispartof | Journal of the American Chemical Society, 2020-05, Vol.142 (20), p.9147-9151 |
| issn | 0002-7863 1520-5126 |
| language | eng |
| recordid | cdi_crossref_primary_10_1021_jacs_0c03763 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biological Products - chemical synthesis Biological Products - chemistry Biological Products - pharmacology Cell Line Cell Proliferation - drug effects Cell Survival - drug effects Drug Screening Assays, Antitumor Humans Molecular Structure |
| title | Synthesis, Cytotoxicity, and Genotoxicity of 10-Aza-9-oxakalkitoxin, an N,N,O‑Trisubstituted Hydroxylamine Analog, or Hydroxalog, of a Marine Natural Product |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T12%3A25%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-acs_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synthesis,%20Cytotoxicity,%20and%20Genotoxicity%20of%2010-Aza-9-oxakalkitoxin,%20an%20N,N,O%E2%80%91Trisubstituted%20Hydroxylamine%20Analog,%20or%20Hydroxalog,%20of%20a%20Marine%20Natural%20Product&rft.jtitle=Journal%20of%20the%20American%20Chemical%20Society&rft.au=Dhanju,%20Sandeep&rft.date=2020-05-20&rft.volume=142&rft.issue=20&rft.spage=9147&rft.epage=9151&rft.pages=9147-9151&rft.issn=0002-7863&rft.eissn=1520-5126&rft_id=info:doi/10.1021/jacs.0c03763&rft_dat=%3Cacs_cross%3Ea110656302%3C/acs_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/32364709&rfr_iscdi=true |